Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care(1) or hospitalization(2-4) after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease. © 2022, The Author(s)

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Semi-continuous summer-season cultivation in a flat outdoor prototype of an autochthonous microalgae for the phytoremediation of urban wastewater at the Ferrara (Italy) plant

Nutrients, like nitrogen (N) and phosphorus (P), released in wastewaters (WW) due to anthropic activities are common pollutants for the environment, since they are usually responsible for the phenomenon of eutrophication of natural wetlands and superficial waters. Similarly WW, mainly urban ones, are often enriched in several micro-organisms, for example coliforms like Escherichia coli, which can cause a wide range of pathologies for humans and animals, beside being increasingly frequently resistant to common antibiotics. Because of their versatility, microalgae are excellent candidates for application in many biotechnological fields, including WW treatment. Results from laboratory-scale experiments on microalgae- based WW treatment are generally promising, while upscaling to outdoor conditions is still in early stages. So, further investigations are needed to improve the applicability of microalgae-based phytoremediation technologies on outdoor plants. This work is focussed on testing the phytoremediation effectiveness with respect to nutrients and E. coli of an autochthonous microalgae strain cultivated in semi- continuous conditions in an 800-L outdoor microalgae prototype placed at the HERA-Ferrara (Italy) WWTP. We assessed, during a summer period, the growth of algae and their potential in nutrients and E. coli removal efficiency (RE) from the effluent deriving from the thickening step of the sludge treatment

Removal of Nitrogen and Phosphorus from Thickening Effluent of an Urban Wastewater Treatment Plant by an Isolated Green Microalga

Microalgae are photosynthetic microorganisms and are considered excellent candidates for a wide range of biotechnological applications, including the removal of nutrients from urban wastewaters, which they can recover and convert into biomass. Microalgae-based systems can be integrated into conventional urban wastewater treatment plants (WW-TP) to improve the water depuration process. However, microalgal strain selection represents a crucial step for effective phytoremediation. In this work, a microalga isolated from the effluent derived from the thickening stage of waste sludge of an urban WW-TP was selected and tested to highlight its potential for nutrient removal. Ammonium and phosphate abatements by microalgae were evaluated using both the effluent and a synthetic medium in a comparative approach. Parallelly, the isolate was characterized in terms of growth capability, morphology, photosynthetic pigment content and photosystem II maximum quantum yield. The isolated microalga showed surprisingly high biomass yield and removal efficiency of both ammonium and phosphate ions from the effluent but not from the synthetic medium. This suggests its clear preference to grow in the effluent, linked to the overall characteristics of this matrix. Moreover, biomass from microalgae cultivated in wastewater was enriched in photosynthetic pigments, polyphosphates, proteins and starch, but not lipids, suggesting its possible use as a biofertilizer

Semi-continuous summer-season cultivation in a flat outdoor prototype of an autochthonous microalgae for the phytoremediation of urban wastewater at the Ferrara (Italy) plant

Nutrients, like nitrogen (N) and phosphorus (P), released in wastewaters (WW) due to anthropic activities are common pollutants for the environment, since they are usually responsible for the phenomenon of eutrophication of natural wetlands and superficial waters. Similarly WW, mainly urban ones, are often enriched in several micro-organisms, for example coliforms like Escherichia coli, which can cause a wide range of pathologies for humans and animals, beside being increasingly frequently resistant to common antibiotics. Because of their versatility, microalgae are excellent candidates for application in many biotechnological fields, including WW treatment. Results from laboratory-scale experiments on microalgae- based WW treatment are generally promising, while upscaling to outdoor conditions is still in early stages. So, further investigations are needed to improve the applicability of microalgae-based phytoremediation technologies on outdoor plants. This work is focussed on testing the phytoremediation effectiveness with respect to nutrients and E. coli of an autochthonous microalgae strain cultivated in semi- continuous conditions in an 800-L outdoor microalgae prototype placed at the HERA-Ferrara (Italy) WWTP. We assessed, during a summer period, the growth of algae and their potential in nutrients and E. coli removal efficiency (RE) from the effluent deriving from the thickening step of the sludge treatment